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Endocr Relat Cancer. 2017 Sep;24(9):T107-T117. doi: 10.1530/ERC-17-0120.

Fighting tubulin-targeting anticancer drug toxicity and resistance.

Author information

1
Institute for the Experimental Endocrinology and Oncology 'G. Salvatore'Italian National Council of Research, Napoli, Italy r.visconti@ieos.cnr.it domenico.grieco@unina.it.
2
Ceinge-Biotecnologie AvanzateNapoli, Italy r.visconti@ieos.cnr.it domenico.grieco@unina.it.
3
Department of Molecular Medicine and Medical BiotechnologiesUniversity of Napoli 'Federico II', Napoli, Italy.

Abstract

Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle. Other possible treatments that improve outcomes in the clinic for these two drug-resistant cancers, including new formulations of the AMCDs and pursuing different molecular targets, will be discussed.

KEYWORDS:

MYT1; WEE1 inhibitor; castration-resistant prostate cancer; mitosis; spindle assembly checkpoint; taxane; triple-negative breast cancer; vinca alkaloids

PMID:
28808045
DOI:
10.1530/ERC-17-0120
[Indexed for MEDLINE]

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